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Many important decisions historically made by people are now made by computers. Algorithms count votes, approve loan and credit card applications, target citizens or neighborhoods for police scrutiny, select taxpayers for IRS audit, grant or deny immigration visas, and more. The accountability mechanisms and legal standards that govern such decision processes have not kept pace with technology. The tools currently available to policymakers, legislators, and courts were developed to oversee human decisionmakers and often fail when applied to computers instead. For example, how do you judge the intent of a piece of software? Because automated decision systems can return potentially incorrect, unjustified, or unfair results, additional approaches are needed to make such systems accountable and governable. This Article reveals a new technological toolkit to verify that automated decisions comply with key standards of legal fairness. We challenge the dominant position in the legal literature that transparency will solve these problems. Disclosure of source code is often neither necessary (because of alternative techniques from computer science) nor sufficient (because of the issues analyzing code) to demonstrate the fairness of a process. Furthermore, transparency may be undesirable, such as when it discloses private information or permits tax cheats or terrorists to game the systems determining audits or security screening. The central issue is how to assure the interests of citizens, and society as a whole, in making these processes more accountable. This Article argues that technology is creating new opportunities—subtler and more flexible than total transparency—to design decisionmaking algorithms so that they better align with legal and policy objectives. Doing so will improve not only the current governance of automated decisions, but also—in certain cases—the governance of decisionmaking in general. The implicit (or explicit) biases of human decisionmakers can be difficult to find and root out, but we can peer into the \"brain\" of an algorithm: computational processes and purpose specifications can be declared prior to use and verified afterward. The technological tools introduced in this Article apply widely. They can be used in designing decisionmaking processes from both the private and public sectors, and they can be tailored to verify different characteristics as desired by decisionmakers, regulators, or the public. By forcing a more careful consideration of the effects of decision rules, they also engender policy discussions and closer looks at legal standards. As such, these tools have far-reaching implications throughout law and society. Part I of this Article provides an accessible and concise introduction to foundational computer science techniques that can be used to verify and demonstrate compliance with key standards of legal fairness for automated decisions without revealing key attributes of the decisions or the processes by which the decisions were reached. Part II then describes how these techniques can assure that decisions are made with the key governance attribute of procedural regularity, meaning that decisions are made under an announced set of rules consistently applied in each case. We demonstrate how this approach could be used to redesign and resolve issues with the State Department's diversity visa lottery. In Part III, we go further and explore how other computational techniques can assure that automated decisions preserve fidelity to substantive legal and policy choices. We show how these tools may be used to assure that certain kinds of unjust discrimination are avoided and that automated decision processes behave in ways that comport with the social or legal standards that govern the decision. We also show how automated decisionmaking may even complicate existing doctrines of disparate treatment and disparate impact, and we discuss some recent computer science work on detecting and removing discrimination in algorithms, especially in the context of big data and machine learning. And lastly, in Part IV, we propose an agenda to further synergistic collaboration between computer science, law, and policy to advance the design of automated decision processes for accountability.

To prevent their being released to the cell exterior, acid hydrolases are recognized by receptors at some point in the secretory pathway and diverted towards the lytic compartment of the cell (lysosome or vacuole). In animal cells, the receptor is called the mannosyl 6-phosphate receptor (MPR) and it binds hydrolase ligands in the trans-Golgi network (TGN). These ligands are then sequestered into clathrin-coated vesicles (CCVs) because of motifs in the cytosolic tail of the MPR which interact first with monomeric adaptors (Golgi-localized, Gammaear-containing, ARF-binding proteins, GGAs) and then with tetrameric (adaptin) adaptor complexes. The CCVs then fuse with an early endosome, whose more acidic lumen causes the ligands to dissociate. The MPRs are then recycled back to the TGN via retromer-coated carriers. Plants have vacuolar sorting receptors (VSRs) which were originally identified in CCVs isolated from pea (Pisum sativum L.) cotyledons. It was therefore assumed that VSRs would have an analogous function in plants to MPRs in animals. Although this dogma has enjoyed wide support over the last 20 years there are many inconsistencies. Recently, results have been published which are quite contrary to it. It now emerges that VSRs and their ligands can interact very early in the secretory pathway, and dissociate in the TGN, which, in contrast to its mammalian counterpart, has a pH of 5.5. Multivesicular endosomes in plants lack proton pump complexes and consequently have an almost neutral internal pH, which discounts them as organelles of pH-dependent receptor–ligand dissociation. These data force a critical re-evaluation of the role of CCVs at the TGN, especially considering that vacuolar cargo ligands have never been identified in them. We propose that one population of TGN-derived CCVs participate in retrograde transport of VSRs from the TGN. We also present a new model to explain how secretory and vacuolar cargo proteins are effectively separated after entering the late Golgi/TGN compartments.

The endoplasmic reticulum (ER) is the gateway to the secretory pathway in all eukaryotic cells. Its products subsequently pass through the Golgi apparatus on the way to the cell surface (true secretion) or to the lytic compartment of the cell (vacuolar protein transport). In animal cells, the Golgi apparatus is present as a stationary larger order complex near the nucleus, and transport between the cortical ER and the Golgi complex occurs via an intermediate compartment which is transported on microtubules. By contrast, higher plant cells have discrete mobile Golgi stacks that move along the cortical ER, and the intermediate compartment is absent. Although many of the major molecular players involved in ER-Golgi trafficking in mammalian and yeast (Saccharomyces cerevisiae) cells have homologs in higher plants, the narrow interface (less than 500 nm) between the Golgi and the ER, together with the motility factor, makes the identification of the transport vectors responsible for bidirectional traffic between these two organelles much more difficult. Over the years, a controversy has arisen over the two major possibilities by which transfer can occur: through vesicles or direct tubular connections. In this article, four leading plant cell biologists attempted to resolve this issue. Unfortunately, their opinions are so divergent and often opposing that it was not possible to reach a consensus. Thus, we decided to let each tell his or her version individually. The review begins with an article by Federica Brandizzi that provides the necessary molecular background on coat protein complexes in relation to the so-called secretory units model for ER-Golgi transport in highly vacuolated plant cells. The second article, written by Chris Hawes, presents the evidence in favor of tubules. It is followed by an article from David Robinson defending the classical notion that transport occurs via vesicles. The last article, by Akihiko Nakano, introduces the reader to possible alternatives to vesicles or tubules, which are now emerging as a result of exciting new developments in high-resolution light microscopy in yeast.

ER lumenal proteins have a K(H)DEL motif at their C-terminus. This is recognized by the ERD2 receptor (KDEL receptor in animals), which localizes to the Golgi apparatus and serves to capture escaped ER lumenal proteins. ERD2-ligand complexes are then transported back to the ER via COPI coated vesicles. The neutral pH of the ER causes the ligands to dissociate with the receptor being returned to the Golgi. According to this generally accepted scenario, ERD2 cycles between the ER and the Golgi, although it has been found to have a predominant Golgi localization. In this short article, we present a model for the functioning of ERD2 receptors in higher plants that explains why it is difficult to detect fluorescently tagged ERD2 proteins in the ER. The model assumes that the residence time for ERD2 in the ER is very brief and restricted to a specific domain of the ER. This is the small disc of ER immediately subjacent to the first cis-cisterna of the Golgi stack, representing specialized ER export and import sites and therefore constituting part of what is known as the ¿secretory unit¿, a mobile aggregate of ER domain plus Golgi stack. ERD2 molecules in the ER domain of the secretory unit may be small in number, transient and optically difficult to differentiate from the larger population of ERD2 molecules in the overlying Golgi stack in the confocal microscope.

Plants constantly adjust their repertoire of plasma membrane proteins that mediates transduction of environmental and developmental signals as well as transport of ions, nutrients, and hormones. The importance of regulated secretory and endocytic trafficking is becoming increasingly clear; however, our knowledge of the compartments and molecular machinery involved is still fragmentary. We used immunogold electron microscopy and confocal laser scanning microscopy to trace the route of cargo molecules, including the BRASSINOSTEROID INSENSITIVE1 receptor and the REQUIRES HIGH BORON1 boron exporter, throughout the plant endomembrane system. Our results provide evidence that both endocytic and secretory cargo pass through the trans-Golgi network/early endosome (TGN/EE) and demonstrate that cargo in late endosomes/multivesicular bodies is destined for vacuolar degradation. Moreover, using spinning disc microscopy, we show that TGN/EEs move independently and are only transiently associated with an individual Golgi stack.

Specimens of a flat and dark brown land planarian were found in a plant nursery in North Carolina, USA in 2020. On the basis of examination of photographs of the live specimens only, the specimens were considered as belonging to Obama nungara , a species originally from South America, which has now invaded a large part of Europe. Unexpectedly, a molecular analysis revealed that the specimens did not belong to this species, neither to the genus Obama . We then undertook its histological study, which finally confirmed that the species is a member of the genus Amaga : the species is herein described as a new species, Amaga pseudobama n. sp. The species has been found in three locations in North Carolina and some infested plants were from Georgia. We reinvestigated specimens collected in Florida in 2015 and found that they also belong to this species. Citizen science observations suggest its presence in other states. Therefore, it is likely that A. pseudobama has already invaded a part of south-east USA and that the invasion took place more than ten years ago. The complete 14,909 bp long mitochondrial genome was obtained. The mitogenome is colinear with those of other Geoplanidae and it was possible to find and annotate a tRNA-Thr, which has been reported missing in several geoplanids. Amaga pseudobama shares with other Geoplaninae the presence of alternative start codons in three protein-coding genes of its mitogenome. The availability of this new genome helped us to improve our annotations of the ND3 gene, for which an ATT start codon is now suggested. Also, the sequence of the ATP6 gene raised questions concerning the use of genetic code 9 to translate the protein-coding genes of Geoplanidae, as the whole translated protein would not contain a single methionine residue when using this code. Two maximum likelihood phylogenies were obtained from genomic data. The first one was based on concatenated alignments of the partial 28S , Elongation Factor 1-alpha ( EF1) and cox1 genes. The second was obtained from a concatenated alignment of the mitochondrial proteins. Both strictly discriminate A. pseudobama from O. nungara and instead associate it with Amaga expatria . We note that the nine species currently accepted within Amaga can be separated into two groups, one with extrabulbar prostatic apparatus, including the type species A. amagensis , and one with intrabulbar prostatic apparatus, including the new species A. pseudobama . This suggests that species of the latter group should be separated from Amaga and constitute a new genus. This finding again illustrates the possible emergence of new invasive species in regions naturally devoid of large land planarians, such as North America. Amaga pseudobama thus deserves to be monitored in the USA, although its superficial resemblance to O. nungara and Geoplana arkalabamensis will complicate the use of photographs obtained from citizen science. Our molecular information provides tools for this monitoring.